Is CABYR p.Thr75Ser (c.223A>T) pathogenic?

CABYR p.Thr75Ser (c.223A>T) is classified Uncertain significance in CABYR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely benign (0.109); Very rare (popmax 0.00171%, amr).

How common is CABYR p.Thr75Ser (c.223A>T) in the general population?

CABYR p.Thr75Ser (c.223A>T) is very rare (popmax 0.00171%, amr) (gnomAD).

What do computational predictors say about CABYR p.Thr75Ser (c.223A>T)?

AlphaMissense predicts likely benign (score 0.109) — an in-silico prediction, not a clinical call.

CABYR p.Thr75Ser

c.223A>T · rs763609438 · VCV2285625

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.109 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00171%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.109	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -5.76	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -3.5
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.21 · regional, not allelic
Overall
CADD	0.274	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00171% Admixed American · 1/58,570 alleles

Filtering AF 0.000502% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.000825% 12/1,453,708 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00171%	58,570
European (non-Finnish)	0.000935%	106,977

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CABYR
Protein: p.Thr75Ser
Coding: c.223A>T
MANE Select: NM_153769
dbSNP: rs763609438
Type: single nucleotide variant
Location: chr18:24155724 (GRCh38)
Gene constraint: LOEUF 1.175 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.43

Full CABYR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CABYR c.541+105G>A Uncertain significance ★ ⚠ same type
CABYR c.541+127C>T Uncertain significance ★ ⚠ same type
CABYR c.541+154A>G Uncertain significance ★ ⚠ same type
CABYR c.541+155A>C Uncertain significance ★ ⚠ same type
CABYR c.541+186G>A Uncertain significance ★ ⚠ same type
CABYR c.541+199C>T Uncertain significance ★ ⚠ same type
CABYR c.541+205C>T Uncertain significance ★ ⚠ same type
CABYR c.541+232C>T Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cabyr-p-thr75ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown